Myelodysplastic syndrome as a late complication following autologous bone marrow transplantation for non-Hodgkin's lymphoma

PURPOSE: To determine the incidence, natural history, and risk factors associated with myelodysplastic syndrome (MDS) occurring as a late complication following autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma. METHODS: We retrospectively reviewed the charts of all 262 patients who underwent autologous bone marrow transplantation for non-Hodgkin's lymphoma at the Dana-Farber Cancer Institute from 1982 through 1991. Although patients received a variety of treatments before they were eligible for transplant, identical myeloablative therapy (cyclophosphamide 60 mg/kg/d for 2 days plus total-body irradiation twice daily for 3 days) was administered in each case. By collecting data on pretransplant and early posttransplant variables, we attempted to identify risk factors for the development of MDS. RESULTS: The crude overall incidence of posttransplant MDS or acute myeloid leukemia (AML) was 7.6%. The actuarial risk at 6 years was 18% +/- 9%. The median time of onset was 31 months (range, 10 to 101) after transplant or 69 months (range, 27 to 141) after initial treatment for lymphoma. Pretreatment variables predictive for the development of MDS (univariate analysis) included prolonged interval between initial treatment and the transplant procedure (P = .003), increased duration of exposure to chemotherapy (P = .019) or to alkylating agents (P = .045), and use of radiation therapy (P = .032) or pelvic radiation (P = .003) before transplant. CONCLUSION: MDS is a potential complication of autologous bone marrow transplantation for non-Hodgkin's lymphoma; bone marrow stem-cell damage sustained before the transplant may be the most important risk factor.     

BB-10010: an active variant of human macrophage inflammatory protein-1 alpha with improved pharmaceutical properties

The stem cell inhibitor, macrophage inflammatory protein-1 alpha (MIP-1 alpha) or LD78, protects multipotent hematopoietic progenitors in murine models from the cytotoxic effects of chemotherapy. Clinical use of human MIP-1 alpha during chemotherapy could therefore lead to faster hematologic recovery and may allow dose intensification. We have also shown that human MIP-1 alpha causes the rapid mobilization of hematopoietic cells, suggesting an additional clinical use in peripheral blood stem cell transplantation. However, the clinical evaluation of human MIP-1 alpha is complicated by its tendency to associate and form high molecular weight polymers. We have produced a variant of rhMIP-1 alpha, BB-10010, carrying a single amino acid substitution of Asp26 > Ala, with a reduced tendency to form large polymers at physiologic pH and ionic strength. This greatly increases its solubility, facilitating its production and clinical formulation. We confirmed the potency of BB-10010 as a human MIP-1 alpha-like agonist in receptor binding, calcium mobilization, inhibition of colony formation, and thymidine suicide assays. The myeloprotective activity of BB-10010 was shown in a murine model of repeated chemotherapy using hydroxyurea. BB-10010 is therefore an ideal variant with which to evaluate the therapeutic potential of recombinant human MIP-1 alpha.     

Changes in mood and hormone levels after rapid-rate transcranial magnetic stimulation (rTMS) of the prefrontal cortex

A person's reality and definition of self are socially constructed; ethnicity is integrally involved in this process. Clinical work is successful if the client constructs a self with a sense of positive self-esteem and empowerment. The profession views social workers' use of self as important in successful clinical work, especially with clients ethnically different from themselves. This article provides a framework adapted from a constructivist perspective for the clinician's skillful use of self in therapeutic discourse. The framework consists of five stances the clinician can use in transcending the discomfort he or she may experience in a cross-cultural clinical situation. Use of these stances facilitates clients' ethnic validation, which is essential to positive therapeutic outcomes. This article uses case examples to illustrate the use of the framework.     

A new approach to the treatment of experimental septic shock

Previous work has shown that disseminated intravascular coagulation (DIC) may produce multiple organ failure, including adult respiratory distress syndrome, by obstruction of visceral micro circulation by microclots DIC can be produced by sepsis. This study tests the ability of a plasminogen activator to prevent death from an intravenous injection of killed Escherichia coli by causing lysis of the microclots. Subjects were two groups of 8 pigs each with body weight of 60-70 lbs. Killed Escherichia coli were injected IV in 16 pigs. Invasive monitoring was used to record physiologic data during the 5.0-hr experimental period. Urokinase injected 20 min after the injection of Escherichia coli organisms significantly prevented mortality, acidosis, and development of blood incoagulability. We conclude that plasminogen activator can significantly prevent fatal Escherichia coli (septic) shock without causing bleeding.     

Clinical features associated with an increased risk of thyroid malignancy in patients with follicular neoplasia by fine-needle aspiration

The trade-off between speed and accuracy and the patterning of movement kinematics have been central issues for theories of human movement for almost a century. In the present contribution experimentally obtained kinematics of reciprocal aiming movements, performed under different task conditions, are modelled as resulting from a single non-linear dynamical system whose parameters vary so as to respond to the task demands. Providing a unified account of speed-accuracy trade-off and trajectory formation phenomena, the model offers a theoretical framework in which both discrete and continuous movements, performed along one or more dimensions can be understood.     

Integrated analysis of diffusion and relaxation of water in blood

A fully validated gas chromatographic-tandem mass spectrometric (GC-MS-MS) method is described for the accurate determination of acetylsalicylic acid (ASA) in human plasma after a single low-dose oral administration of aspirin or guaimesal, an ASA releasing prodrug. ASA and the newly prepared O-[2H3]-acetylsalicylic acid (d3-ASA) used as internal standard were determined in 100-microl aliquots of plasma by extractive pentafluorobenzyl (PFB) esterification using PFB bromide and tetrabutylammoniumhydrogen sulphate as the esterifying and ion-pairing agent, respectively, and by GC-MS-MS analysis in the negative-ion chemical ionization mode. The overall relative standard deviations were below 8% for ASA levels in the range 0-1 microg/ml plasma. Mean accuracy was 3.8% for ASA levels within the range 0-100 ng/ml. The limit of quantitation of the method was determined as 200 pg/ml ASA at an accuracy of 5.5% and a precision of 15.2%. The limit of detection was determined as 546 amol of ASA at a signal-to-noise ratio of 10:1.